Process and intermediate

Patent metadata

Field	Value
Publication number	US-11136289-B2
Application number	US-202016884231-A
Country	US
Kind code	B2
Filing date	May 27, 2020
Priority date	Jul 22, 2016
Publication date	Oct 5, 2021
Grant date	Oct 5, 2021

Abstract

Process for the preparation of a compound of Formula (I):the process comprising the reaction of a compound of Formula (II) with malononitrile in the presence of a base and a palladium catalyst,wherein X, Y and Z, independently of each other, represent fluoro, chloro or C1-4alkyl; and L is a leaving group; with the proviso that 1 or 2 of X and Y are, independently of each other, fluoro or chloro.

First claim

The invention claimed is:

1. A process, comprising:
reacting a compound of Formula (I)

wherein
X, Y and Z, independently of each other, represent fluoro, chloro or C 1-4 alkyl, and with the proviso that 1 or 2 of X and Y are, independently of each other, fluoro or chloro;
with an acid in the presence of water, and a hydrocarbon solvent to form a compound of Formula (III)

2. The process of claim 1 , wherein the hydrocarbon solvent is benzene.

3. The process of claim 1 , wherein the hydrocarbon solvent is mesitylene.

4. The process of claim 1 , wherein the hydrocarbon solvent is xylene.

5. The process of claim 1 , wherein the hydrocarbon solvent is toluene.

6. The process of claim 1 , wherein the solvent is an aromatic hydrocarbon solvent.

7. The process of claim 6 , wherein the reacting of the compound of Formula (I) to form the compound of Formula (III) is under distillation conditions.

8. The process of claim 6 , wherein the water and aromatic hydrocarbon solvent form an azeotrope.

9. The process of claim 6 , wherein the reacting of the compound of Formula (I) to form the compound of Formula (III) is at a temperature of 120 to 155° C.

10. The process of claim 6 , wherein the reacting of the compound of Formula (I) to form the compound of Formula (III) is at increased pressure.

11. The process of claim 1 , wherein X, Y, and Z are defined as follows:

X
Y
Z

CH 3
F
CH 3

CH 3
Cl
CH 3

F
CH 3
CH 3

Cl
CH 3
CH 3

F
F
CH 3

Cl
Cl
CH 3 .

12. The process of claim 11 , wherein X is CH 3 , Y is Cl, and Z is CH 3 .

13. A process, comprising:
preparing a reaction vessel with solid sodium hydroxide and an inert atmosphere;
adding a dipolar aprotic solvent to the reaction vessel;
cooling the reaction vessel containing the dipolar aprotic solvent and solid sodium hydroxide and adding malononitrile to the reaction vessel;
adding 2-bromo-5-chloro-1,3-dimethyl-benzene to the reaction vessel; and
adding a mixture containing palladium (II) and a second dipolar aprotic solvent to the reaction vessel and forming 2-(4-chloro-2,6-dimethyl-phenyl)propanedinitrile.

14. The process of claim 13 , wherein cooling is below room-temperature.

15. The process of claim 14 , further comprising distilling off the dipolar aprotic solvent after cooling.

16. The process of claim 15 , wherein the dipolar aprotic solvent and the second dipolar aprotic solvent are selected from at least one of N,N-dimethylformamide, dimethyl sulfoxide, N-methyl-2-pyrrolidone, N,N-dimethylacetamide, and N,N′-dimethylethyleneurea.

17. The process of claim 16 , wherein the dipolar aprotic solvent and the second dipolar aprotic solvent are N-methyl-2-pyrrolidone and the temperature of the reaction vessel is between 80 to 170° C. when the reaction vessel contains 2-bromo-5-chloro-1,3-dimethyl-benzene and the palladium (II) catalyst.

18. The process of claim 1 , further comprising reacting the compound of Formula (III) with a compound of Formula (V),

wherein R 1 is C 1-4 alkoxy, a compound of formula (VI),

wherein R 2 is phenyl or phenyl substituted by one or more substituents selected from the group consisting of C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, halogen and nitro, and an amine of formula A-NH 2 , wherein A is C 1-4 alkyl, to form a compound of Formula (IV),

reacting the compound of formula (IV) with a base to form a compound of Formula (VII),

and
reacting the compound of Formula (VII) with an acid halide to form a compound of Formula (VIII),

wherein G is C(O)R, and R is C 1-4 alkoxy.

19. The process of claim 18 , wherein:
X is CH 3 , Y is Cl, and Z is CH 3 ;
A is methyl;
R 1 is methoxy; and
R is ethoxy.

Assignees

• Syngenta Participations Ag

Inventors

• Zeller Martin
• Fedou Nicolas

Classifications

• C07C255/35 Primary

  the carbon skeleton being further substituted by halogen atoms, or by nitro or nitroso groups · CPC title

• C07C255/33

  with cyano groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by saturated carbon chains · CPC title

• C07C253/30 Primary

  by reactions not involving the formation of cyano groups · CPC title

• C07C53/134

  monocyclic · CPC title

• C07C51/08

  from nitriles · CPC title